Autologous CD19CAR-T Therapy for Recurrent/Refractory Autoimmune Diseases

NCT06993493 | Recruiting

• 1 other identifier: BRYY-IIT-LCYJ-2024-020
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single center, open label exploratory clinical trial aimed at evaluating the safety and efficacy of autologous CD19 CAR-T therapy in subjects with autoimmune diseases. The study will adopt the traditional dose escalation model "3+3" design, with three dose groups set up, starting at a dose of 0.5 × 106 CAR+T cells/kg, to observe DLT, and conduct a 24 month safety and efficacy follow-up after cell infusion to observe the safety of autologous CD19 CAR-T and conduct preliminary efficacy evaluation. Three dose groups were set up, with dose group 1 as the starting dose, following the traditional 3+3 design rule for a single intravenous infusion: Dose group dosage unit (CAR+T cells/kg) Acceptable dose range Expected sample size (± 30%, CAR+T cells/kg)

1. 1.0.5 × 106 0.4 × 106\~0.6 × 106 3-6 cases
2. 2.1.0 × 106 0.7 × 106\~1.3 × 106 3-6 cases
3. 3.2.0 × 106 1.4 × 106\~2.6 × 106 3-6 cases Dose escalation rule The enrollment starts from dose group 1, and if no DLT occurs in the 3 subjects included, they will be transferred to the next dose group. If one of the three subjects in a certain dose group develops DLT, three additional subjects will be added to the group for cell infusion at the same dose. If there is ≥ 1 case of DLT in the 3 additional cases, it will be reduced to the previous dose group. If there are only 3 subjects in the previous dose group at this time, an additional 3 subjects need to be added for the trial; If there are already 6 subjects in the previous dose group, the trial ends and this dose is the maximum tolerated dose (MTD).

Conditions

Autoimmune Disease

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  0~28 day after treatment

Study Arms (1)

CD19 CART

EXPERIMENTAL

Genetic: CD19 CART

Interventions

CD19 CART GENETIC

The dose escalation is carried out according to the principle of "3+3" escalation, with a total of 3 dose groups set up. Expected sample size (± 30%, CAR+T cells/kg) 1. 0.5 × 106 0.4 × 106\~0.6 × 106 3-6 cases 2. 1.0 × 106 0.7 × 106\~1.3 × 106 3-6 cases 3. 2.0 × 106 1.4 × 106\~2.6 × 106 3-6 cases The enrollment starts from dose group 1, and if no DLT occurs in the 3 subjects included, they will be transferred to the next dose group. If one of the three subjects in a certain dose group develops DLT, three additional subjects will be added to the group for cell infusion at the same dose. If there is ≥ 1 case of DLT in the 3 additional cases (i.e. ≥ 2/6 cases in this dose group), it will be reduced to the previous dose group. If there are only 3 subjects in the previous dose group at this time, an additional 3 subjects need to be added for the trial; If there are already 6 subjects in the previous dose group, the trial ends and this dose is MTD.

CD19 CART

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range of 18 to 65 years old (including 18 and 65 years old), gender is not limited;
• Special criteria for different indications:
• Subjects with relapsed/refractory moderate to severe SLE must meet the following criteria:
• According to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria, the diagnosis is SLE;
• Positive for anti nuclear antibody (ANA) (titer ≥ 1:80), and/or positive for anti dsDNA antibody, and/or positive for anti Sm antibody during screening;
• The definition of moderate to severe activity is: SLEDAI-2000 score ≥ 8 during screening; If there is a low complement and/or anti dsDNA antibody score, the clinical symptom score for SLEDAI-2000 (excluding low complement and/or anti dsDNA antibodies) must be ≥ 6 points;
• At least 6 months of stable standard treatment have been used in the SLE history prior to screening, and the condition remains active for at least 2 months prior to screening. The standard treatment plan refers to the stable use of any of the following drugs (used alone or in combination): glucocorticoids (≤ 20mg/day prednisone or equivalent), antimalarials (hydroxychloroquine ≤ 400mg/day, chloroquine ≤ 500mg/day), nonsteroidal anti-inflammatory drugs (NSAIDs), biologics (rituximab, belimumab, tacept), and other immunosuppressants or immunomodulators, including mycophenolate mofetil (≤ 2g/day), azathioprine (≤ 2mg/kg/day), methotrexate (≤ 20mg/week), etc;
• Recurrent/refractory dcSSc subjects must meet the following criteria:
• According to the 2013 EULAR/ACR classification criteria for systemic sclerosis (SSc), the diagnosis is SSc;
• According to the definition criteria of LeRoy et al. in 1988, it meets the diffuse skin type presentation, which refers to extensive skin fibrosis and involvement of the skin near the elbow and/or knee;
• When screening, interstitial lung disease (ILD) should be included, and 45% of the predicted values should be ≤ forced vital capacity (FVC) ≤ 70% of the predicted values, or 40% of the predicted values should be ≤ diffusion capacity of carbon monoxide (DLCO) ≤ 70% of the predicted values;
• Relapse/refractory is defined as: recurrence after previous ineffective conventional treatment or disease remission. Conventional treatment refers to the use of glucocorticoids, cyclophosphamide, and at least one immunosuppressive/regulatory drug for at least 6 months. Immunosuppressive/regulatory drugs include azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, rituximab, belimumab, tacrolizumab, etc;
• Activity is defined as having at least one of the following:
• There is evidence of skin progression during screening, that is, an increase of ≥ 10% in mRSS scores within the past 6 months;
• During screening, there is evidence of any of the following ILD activities:

You may not qualify if:

• Patients with previous or concurrent active malignant tumors, including tumor associated polymyositis/dermatomyositis. Cervical carcinoma in situ that has been cured or has not recurred for at least 2 years, non-invasive basal cell or squamous cell skin cancer, locally treated prostate cancer, and ductal carcinoma in situ after radical surgery are excluded;
• Within the past 3 months, severe pulmonary diseases such as moderate to severe pulmonary arterial hypertension (average pulmonary arterial pressure detected by echocardiography\>60 mmHg) require oxygen mask therapy or non-invasive or invasive ventilator assisted breathing during screening; During screening, IgA, IgG, and IgM levels were below the lower limit of normal (LLN);
• Patients who have used any of the following medications or treatments within the specified time:
• Individuals who have used B-cell depletion therapy within the previous month and have not failed treatment as assessed by clinical physicians, including those targeting CD20, CD22, CD52, CD38, BCMA monoclonal antibodies, or bispecific antibodies;
• Screening for excessive use of human intravenous immunoglobulin within the previous month;
• Use therapeutic doses of corticosteroids (prednisone ≥ 20mg/day or equivalent doses of other corticosteroids) within 24 hours prior to Qinglin pretreatment;
• Received corticosteroid shock therapy within 2 weeks (defined as a dose ≥ 500mg/d of prednisone or equivalent dose of other corticosteroids);
• Received tacrolizumab within 2 weeks prior to screening, or received belimumab within 3 weeks;
• Patients with a history of severe central nervous system diseases or related symptoms (excluding simple trigeminal nerve disease) within the past 6 months, including but not limited to: lupus encephalopathy, cerebrovascular disease, encephalitis, brain injury, aneurysm, cerebellar disease, organic brain syndrome, Parkinson's disease and other central nervous system diseases, as well as epilepsy, seizures, aphasia, dementia and other symptoms;
• Individuals who have experienced lupus crisis within the previous 3 months, such as active central nervous system lupus, severe hemolytic anemia, severe thrombocytopenic purpura, severe neutropenia, severe myocardial injury, severe lupus pneumonia or pulmonary hemorrhage, severe lupus hepatitis, severe vasculitis, etc;
• Concurrent severe kidney disease: severe lupus nephritis (defined as urinary protein\>4g/24 hours or serum creatinine\>1.5 × ULN or creatinine clearance rate (Cockcroft Gault formula)\<30 mL/min) within the first 8 weeks of screening, Or active nephritis that requires treatment with drugs prohibited by the protocol, or requires treatment with prednisone greater than 500mg/day or equivalent corticosteroids for ≥ 14 days;
• Those who have severe allergies to the Qinglin pre-treatment drugs and any components of autologous CD19 CAR-T used in this study;
• hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV DNA positive; Individuals with positive hepatitis C virus (HCV) antibodies and positive HCV RNA; Positive for Treponema pallidum antibody; HIV antibody positive individuals;
• There are uncontrolled fungi, bacteria, viruses, or other infections that researchers have assessed as unsuitable for participation in the study;
• History of major organ transplantation (such as heart and lung); During screening, there is active tuberculosis or latent tuberculosis (referring to whether the tuberculin skin test or interferon test is positive, and there are no clinical symptoms or imaging evidence);

Sponsors & Collaborators

• Beijing Boren Hospital: lead

Study Sites (1)

Beijing Gobroad Brond Hospital

Beijing, Beijing Municipality, 100070, China

RECRUITING

MeSH Terms

Conditions

Autoimmune Diseases

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• yajing zhang, MD/PhD

  Beijing Gaobo Boren Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

yajing zhang, MD/PhD

CONTACT

+8601083605002(716); zhangyj3@gobroadhealthcare.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2025
• First Posted: May 28, 2025
• Study Start: February 20, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: May 28, 2025

Record last verified: 2024-08

Locations

CN (1)